It is proposed that alcoholics are characterized by large conditioned compensatory responses, opposite in direction to the effect of alcohol, to alcohol related cues. This response is thought to play a major role in the etiology of alcoholism and in relapse. The classical conditioning model of drug dependency has been extensively supported in the animal literature. Pilot data from this laboratory represents the first controlled evidence of the conditioned compensatory response in human subjects, which consisted of decreased pulse transmission time ("pounding heart") and decreased fingers skin temperature and finger pulse amplitude ("cold hands"). The proposed research provides a critical test of the conditioned compensatory response to alcohol cues in human subjects, and assesses its significance in the etiology of alcoholism. The first proposed experiment is a within-subject realization of the balanced placebo design using autonomic measures of the response to alcohol and the conditioned compensatory response. Sixteen male social drinkers will have repeated pairings of alcohol with one distinctive room and placebo with a different room. Subsequent testing with placebo in the alcohol room is expected to replicate the conditioned compensatory response found in pilot data, and testing with alcohol in the placebo room is expected to show loss of tolerance. The second experiment compares the magnitude of the conditioned compensatory response in nonalcoholic social drinkers with and without familial alcoholism and scoring high and low on a personality risk factor for alcoholism. Subjects at risk for alcoholism are expected to show larger conditioned compensatory responses to alcohol-related cues (e.g., placebo administered in a room previously paired with alcohol). The research has important implications for the etiology of alcohol dependency, selection of a at risk individuals for primary prevention, and the prevention of relapse in alcoholics using cue exposure therapy.